Polyarylether membranes

ABSTRACT

Membranes for use in methods and apparatuses for hemodialysis and hemofiltration are composed of at least one membrane comprising a polyarylethernitrile having structural units of formula 1, 2, 3 and 4 
                         
wherein
         Z is a direct bond, O, S, CH 2 , SO, SO 2 , CO, RPO, CH 2 , alkenyl, alkynyl, a C 1 -C 12  aliphatic radical, a C 3 -C 12  cycloaliphatic radical, a C 3 -C 12  aromatic radical or a combination thereof;   R is a C 6-12  aromatic radical or a C 1-12  aliphatic radical;   R 1  and R 2  are independently H, halo, nitro, a C 1 -C 12  aliphatic radical, a C 3 -C 12  cycloaliphatic radical, a C 3 -C 12  aromatic radical, or a combination thereof;   a is 0, 1, 2 or 3;   b is 0, 1, 2, 3 or 4;   m and n are independently 0 or 1; and   Q and Z are different.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to U.S. patent application Ser. Nos.11/567,487 filed Dec. 6, 2006 and 11/611,691 filed Dec. 15, 2006.

BACKGROUND

The invention relates generally to methods and apparatuses forhemodialysis and hemofiltration.

In recent years, porous membranes, either in hollow fiber or flat sheetconfigurations have found use in hemodialysis and hemofiltration.Hemodialysis membranes are porous membranes permitting the passage oflow molecular weight solutes, typically less than 5,000 Daltons, such asurea, creatinine, uric acid, electrolytes and water, yet preventing thepassage of higher molecular weight proteins and blood cellular elements.Hemofiltration, which more closely represents the filtration in theglomerulus of the kidney, requires even more permeable membranesallowing complete passage of solutes of molecular weight of less than50,000 Daltons, and, in some cases, less than 20,000 Daltons. Thepolymers used in these membranes must possess excellent mechanicalproperties so as to support the fragile porous membrane structure duringmanufacture and use. In addition, the polymer must have adequate thermalproperties so as not to degrade during high temperature steamsterilization processes. Furthermore these membranes must have excellentbiocompatibility, such that protein fouling is minimized and thrombosisof the treated blood does not occur. Though polysulfones have themechanical and thermal properties necessary for these applications, theyare insufficiently hydrophilic. To improve their hydrophilicity,polysulfones have been blended with hydrophilic polymers such aspolyvinylpyrollidinone (PVP). However, since PVP is water soluble it isslowly leached from the porous polymer matrix creating productvariability. Notwithstanding, the method of blending polysulfone with ahydrophilic polymer such as PVP is a commercially used process forproducing hydrophilic porous polysulfone membranes for hemofiltrationand hemodialysis.

Thus porous membranes possessing excellent thermal and mechanicalproperties and excellent biocompatibility for hemodialysis andhemofiltration are desired. In addition, polymers capable of beingfabricated into porous membranes that possess sufficient hydrophilicityto obviate the need for blending with a hydrophilic polymers is alsodesired. Finally polymers which are more hydrophilic than polysulfoneyet not water soluble, which may induce hydrophilicity to the porouspolysulfone membranes without undesirably leaching from the membrane arealso sought.

BRIEF DESCRIPTION

In one aspect, the present invention relates to polyethernitrile blockcopolymers comprising structural units of formula I

wherein

-   -   Z is a direct bond, O, S, CH₂, SO, SO₂, CO, phenylphosphine        oxide or a combination thereof;    -   R¹ and R² are independently H, halo, cyano, nitro, a C₁-C₁₂        aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂        aromatic radical, or a combination thereof;    -   a is 0, 1, 2 or 3;    -   b is 0, 1, 2, 3 or 4; and    -   m and n are independently 0 or 1.

In another aspect, the present invention relates to porous membranescomposed of the polyarylethernitrile block copolymer of the presentinvention.

In another aspect, the present invention relates to methods forhemodialysis or hemofiltration, said method comprising contacting bloodwith a porous membrane according to the present invention. In anotheraspect, the present invention relates to a dialysis apparatus thatincludes a plurality of porous hollow fibers composed of the porousmembranes of the present invention.

DETAILED DESCRIPTION

Hemodialysis is a process for removing substances through the blood bytheir unequal penetration through a permeable membrane. Hemodialysismembranes permit the passage of low molecular weight solutes, typicallyless than 5,000 Daltons, such as urea, creatinine, uric acid,electrolytes and water, but prevent the passage of higher molecularweight proteins and blood cellular elements. Hemofiltration, which moreclosely represents the filtration in the glomerulus of the kidney,requires more highly permeable membranes which allow complete passage ofsolutes of molecular weight of less than 50,000 Daltons, and, in somecases, less than 20,000 Daltons. Most dialyzers in use are of a hollowfiber design though designs employing flat sheet membranes are alsocommercially available with blood and dialysate generally flowing inopposite directions. Both methods comprise contacting blood with aporous hollow fiber membrane.

The porous membranes of the present invention are composed of at leastone polyarylethernitrile block copolymer having structural units offormula I. In particular embodiments, the porous membrane may be ahollow fiber or in a flat sheet configuration.

The block copolymers may additionally include at least one block havingstructural units of formula II

wherein

-   -   R³, R⁴ and R⁵ are independently H, halo, nitro, a C₁-C₁₂        aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂        aromatic radical or a combination thereof;    -   Q is a direct bond, O, S, CH₂, alkenyl, alkynyl, a C₁-C₁₂        aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂        aromatic radical or a combination thereof;    -   Z¹ is a direct bond, O, S, CH₂, SO, SO₂, CO, RPO or a        combination thereof,    -   c, d and e are independently 0, 1, 2, 3 or 4; and    -   p, q and r are independently 0 or 1.

In a particular embodiment, the polyarylethernitrile block copolymerincludes structural units of formula IA, and, in yet another particularembodiment, the polyarylethernitrile block copolymer includes structuralunits of formula IA and IIA

In another particular embodiment, the polyarylethernitrile blockcopolymer includes structural units of formula IA, and, in yet anotherparticular embodiment, the polyarylethernitrile block copolymer includesstructural units of formula IA and IIAIIB

In another aspect, the present invention relates to membranes composedof random polyarylethernitrile copolymers having structural units offormula 1, 2, 3 and 4

wherein

-   -   Z is a direct bond, O, S, CH₂, SO, SO₂, CO, RPO, CH₂, a C₁-C₁₂        aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂        aromatic radical or a combination thereof;    -   R is a C₆₋₁₂ aromatic radical or a C₁₋₁₂ aliphatic radical;    -   R¹ and R² are independently H, halo, nitro, a C₁-C₁₂ aliphatic        radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂ aromatic        radical, or a combination thereof;    -   a is 0, 1, 2 or 3;    -   b is 0, 1, 2, 3 or 4;    -   m and n are independently 0 or 1; and    -   Q and Z are different.

In a particular embodiment, the random polyarylethernitrile copolymerincludes structural units of formula 1A, 2A, and 3A

In another particular embodiment, the polyarylethernitrile comprisesstructural units of formula 1A, 2A, and 3B

Polyarylethernitriles are typically solvent resistant polymers with highglass transition temperature and/or melting point.

The polyarylethernitrile block copolymers and randompolyarylethernitrile copolymers may be produced by reacting at least onedihalobenzonitrile with at least one aromatic dihydroxy compound in apolar aprotic solvent in the presence of an alkali metal compound, andoptionally, in the presence of catalysts. Other dihalo aromaticcompounds in addition to the dihalobenzonitrile may also be used.

Some examples of the dihalobenzonitrile monomers useful for preparingthe polyarylethernitrile block copolymers and randompolyarylethernitrile copolymers of the present invention include2,6-dichlorobenzonitrile, 2,6-difluorobenzonitrile,2,5-dichlorobenzonitrile, 2,5-difluorobenzonitrile2,4-dichlorobenzonitrile, and 2,4-difluorobenzonitrile.

Exemplary dihalo aromatic compounds that may be used include4,4′-bis(chlorophenyl)sulfone, 2,4′-bis(chlorophenyl)sulfone,2,4-bis(chlorophenyl)sulfone, 4,4′-bis(fluorophenyl)sulfone,2,4′-bis(fluorophenyl)sulfone, 2,4-bis(fluorophenyl)sulfone,4,4′-bis(chlorophenyl)sulfoxide, 2,4′-bis(chlorophenyl)sulfoxide,2,4-bis(chlorophenyl)sulfoxide, 4,4′-bis(fluorophenyl)sulfoxide,2,4′-bis(fluorophenyl)sulfoxide, 2,4-bis(fluorophenyl)sulfoxide,4,4′-bis(fluorophenyl)ketone, 2,4′-bis(fluorophenyl)ketone,2,4-bis(fluorophenyl)ketone, 1,3-bis(4-fluorobenzoyl)benzene,1,4-bis(4-fluorobenzoyl)benzene, 4,4′-bis(4-chlorophenyl)phenylphosphineoxide, 4,4′-bis(4-fluorophenyl)phenylphosphine oxide,4,4′-bis(4-fluorophenylsulfonyl)-1,1′-biphenyl,4,4′-bis(4-chlorophenylsulfonyl)-1,1′-biphenyl,4,4′-bis(4-fluorophenylsulfoxide)-1,1′-biphenyl, and4,4′-bis(4-chlorophenylsulfoxide)-1,1′-biphenyl.

Suitable aromatic dihydroxy compounds that may used to make thepolyarylethernitrile block copolymers and random polyarylethernitrilecopolymers include 4,4′-dihydroxyphenyl sulfone, 2,4′-dihydroxyphenylsulfone, 4,4′-dihydroxyphenyl sulfoxide, 2,4′-dihydroxyphenyl sulfoxide,bis(3,5-dimethyl-4-hydroxyphenyl) sulfoxide,bis(3,5-dimethyl-4-hydroxyphenyl) sulfone,4,4-(phenylphosphinyl)diphenol, 4,4′-oxydiphenol,4,4′-thiodiphenol,4,4′-dihydroxybenzophenone, 4,4′dihydroxyphenylmethane, hydroquinone,resorcinol, 5-cyano-1,3-dihydroxybenzene, 4-cyano-1,3,-dihydroxybenzene,2-cyano-1,4-dihydroxybenzene, 2-methoxyhydroquinone, 2,2′-biphenol,4,4′-biphenol, 2,2′-dimethylbiphenol 2,2′,6,6′-tetramethylbiphenol,2,2′,3,3′,6,6′-hexamethylbiphenol,3,3′,5,5′-tetrabromo-2,2′6,6′-tetramethylbiphenol,4,4′-isopropylidenediphenol (bisphenol A),4,4′-isopropylidenebis(2,6-dimethylphenol) (teramethylbisphenol A),4,4′-isopropylidenebis(2-methylphenol),4,4′-isopropylidenebis(2-allylphenol),4,4′-isopropylidenebis(2-allyl-6-methylphenol),4,4′(1,3-phenylenediisopropylidene)bisphenol (bisphenol M),4,4′-isopropylidenebis(3-phenylphenol),4,4′-isopropylidene-bis(2-phenylphenol),4,4′-(1,4-phenylenediisoproylidene)bisphenol (bisphenol P),4,4′-ethylidenediphenol (bisphenol E), 4,4′-oxydiphenol,4,4′-thiodiphenol, 4,4′-thiobis(2,6-dimethylphenol),4,4′-sufonyldiphenol, 4,4′-sufonylbis(2,6-dimethylphenol)4,4′-sulfinyldiphenol, 4,4′-hexafluoroisoproylidene)bisphenol (BisphenolAF), 4,4′-hexafluoroisoproylidene) bis(2,6-dimethylphenol),4,4′-(1-phenylethylidene)bisphenol (Bisphenol AP),4,4′-(1-phenylethylidene)bis(2,6-dimethylphenol),bis(4-hydroxyphenyl)-2,2-dichloroethylene (Bisphenol C),bis(4-hydroxyphenyl)methane (Bisphenol-F),bis(2,6-dimethyl-4-hydroxyphenyl)methane,2,2-bis(4-hydroxyphenyl)butane, 3,3-bis(4-hydroxyphenyl)pentane,4,4′-(cyclopentylidene)diphenol, 4,4′-(cyclohexylidene)diphenol(Bisphenol Z), 4,4′-(cyclohexylidene)bis(2-methylphenol),4,4′-(cyclododecylidene)diphenol,4,4′-(bicyclo[2.2.1]heptylidene)diphenol,4,4′-(9H-fluorene-9,9-diyl)diphenol,3,3′-bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one,1-(4-hydroxyphenyl)-3,3′-dimethyl-2,3-dihydro-1H-inden-5-ol,1-(4-hydroxy-3,5-dimethylphenyl)-1,3,3′,4,6-pentamethyl-2,3-dihydro-1H-inden-5-ol,3,3,3′,3′-tetramethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[indene]-5,6′-diol(Spirobiindane), dihydroxybenzophenone (bisphenol K), thiodiphenol(Bisphenol S), bis(4-hydroxyphenyl) diphenyl methane,bis(4-hydroxyphenoxy)-4,4′-biphenyl, 4,4′-bis(4-hydroxyphenyl)diphenylether, 9,9-bis(3-methyl-4-hydroxyphenyl) fluorene, andN-phenyl-3,3-bis-(4-hydroxyphenyl)phthalimide.

In particular embodiments, one of a or b may be 0. In specificembodiments, both a and b are 0, and the polyarylethernitrile blockcopolymers and random polyarylethernitrile copolymers are composed ofunsubstituted structural units, except for the nitrile substituent.

A basic salt of an alkali metal compound may be used to effect thereaction between the dihalo and dihydroxy aromatic compounds, and is notparticularly limited so far as it can convert the aromatic dihydroxycompound to its corresponding alkali metal salt. Exemplary compoundsinclude alkali metal hydroxides, such as, but not limited to, lithiumhydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide,and cesium hydroxide; alkali metal carbonates, such as, but not limitedto, lithium carbonate, sodium carbonate, potassium carbonate, rubidiumcarbonate, and cesium carbonate; and alkali metal hydrogen carbonates,such as but not limited to lithium hydrogen carbonate, sodium hydrogencarbonate, potassium hydrogen carbonate, rubidium hydrogen carbonate,and cesium hydrogen carbonate. Combinations of compounds may also beused to effect the reaction.

Some examples of the aprotic polar solvent that may be effectively usedto make the polyarylethernitrile include N,N-dimethylformamide,N,N-diethylformamide, N,N-dimethylacetamide, N,N-diethylacetamide,N,N-dipropylacetamide, N,N-dimethylbenzamide, N-methyl-2-pyrrolidone(NMP), N-ethyl-2-pyrrolidone, N-isopropyl-2-pyrrolidone,N-isobutyl-2-pyrrolidone, N-n-propyl-2-pyrrolidone,N-n-butyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone,N-methyl-3-methyl-2-pyrrolidone, N-ethyl-3-methyl-pyrrolidone,N-methyl-3,4,5-trimethyl-2-pyrrolidone, N-methyl-2-piperidone,N-ethyl-2-piperidone, N-isopropyl-2-piperidone,N-methyl-6-methyl-2-piperidone, N-methyl-3-ethylpiperidone,dimethylsulfoxide (DMSO), diethylsulfoxide, sulfolane,1-methyl-1-oxosulfolane, 1-ethyl-1-oxosulfolane,1-phenyl-1-oxosulfolane, N,N′-dimethylimidazolidinone (DMI),diphenylsulfone, and combinations thereof. The amount of solvent to beused is typically an amount that is sufficient to dissolve the dihaloand dihydroxy aromatic compounds.

The reaction may be conducted at a temperature ranging from about 100°C. to about 300° C., ideally from about 120 to about 200° C., morepreferably about 150 to about 200° C. Often when thermally unstable orreactive groups are present in the monomer and wish to be preserved inthe polymer, temperatures in the regime of about 100 to about 120° C.,in other embodiments from about 110 to about 145° C. is preferred. Thereaction mixture is often dried by addition to the initial reactionmixture of, along with the polar aprotic solvent, a solvent that formsan azeotrope with water. Examples of such solvents include toluene,benzene, xylene, ethylbenzene and chlorobenzene. After removal ofresidual water by azeotropic drying, the reaction is carried out at theelevated temperatures described above. The reaction is typicallyconducted for a time period ranging from about 1 hour to about 72 hours,ideally about 1 hour to about 10 hours. Alternatively the bisphenol isconverted in an initial step to its dimetallic phenolate salt andisolated and dried. The anhydrous dimetallic salt is used directly inthe condensation polymerization reaction with a dihaloaromatic compoundin a solvent, either a halogenated aromatic or polar aprotic, attemperatures from about 120 to about 300° C. The reaction may be carriedout under ordinary pressure or pressurized conditions.

When halogenated aromatic solvents are used phase transfer catalysts maybe employed. Suitable phase transfer catalysts includehexaalkylguanidinium salts and bis-guanidinium salts. Typically thephase transfer catalyst comprises an anionic species such as halide,mesylate, tosylate, tetrafluoroborate, or acetate as thecharge-balancing counterion(s). Suitable guanidinium salts include thosedisclosed in U.S. Pat. Nos. 5,132,423; 5,116,975 and 5,081,298. Othersuitable phase transfer catalysts include p-dialkylamino-pyridiniumsalts, bis-dialkylaminopyridinium salts, bis-quaternary ammonium salts,bis-quaternary phosphonium salts, and phosphazenium salts. Suitablebis-quaternary ammonium and phosphonium salts are disclosed in U.S. Pat.No. 4,554,357. Suitable aminopyridinium salts are disclosed in U.S. Pat.No. 4,460,778; U.S. Pat. No. 4,513,141 and U.S. Pat. No. 4,681,949.Suitable phosphazenium salts are disclosed in U.S. patent applicationSer. No. 10/950,874. Additionally, in certain embodiments, thequaternary ammonium and phosphonium salts disclosed in U.S. Pat. No.4,273,712 may also be used.

The dihalobenzonitrile or mixture of dihalobenzonitriles or mixture ofdihalobenzonitrile and a dihalo aromatic compound may be used insubstantially equimolar amounts relative to the dihydroxy aromaticcompounds or mixture of dihydroxy aromatic compounds used in thereaction mixture. The term “substantially equimolar amounts” means amolar ratio of the dihalobenzonitrile compound(s) to dihydroxy aromaticcompound(s) is about 0.85 to about 1.2, preferably about 0.9 to about1.1, and most preferably from about 0.98 to about 1.02.

After completing the reaction, the polymer may be separated from theinorganic salts, precipitated into a non-solvent and collected byfiltration and drying. The drying may be carried out either under vacuumand/or at high temperature, as is known commonly in the art. Examples ofnon-solvents include water, methanol, ethanol, propanol, butanol,acetone, methyl ethyl ketone, methyl isobutyl ketone,gamma.-butyrolactone, and combinations thereof. Water and methanol arethe preferred non-solvents.

The glass transition temperature, T_(g), of the polymer typically rangesfrom about 120° C. to about 280° C. in one embodiment, and ranges fromabout 140° C. to about 200° C. in another embodiment. In some specificembodiments, the T_(g) ranges from about 140° C. to about 190° C., whilein other specific embodiments, the T_(g) ranges from about 150° C. toabout 180° C.

The polyarylethernitrile may be characterized by number averagemolecular weight (M_(n)) and weight average molecular weight (M_(w)).The various average molecular weights M_(n) and M_(w) are determined bytechniques such as gel permeation chromatography, and are known to thoseof ordinary skill in the art. In one embodiment, the M_(n) of thepolymer may be in the range from about 10,000 grams per mole (g/mol) toabout 1,000,000 g/mol. In another embodiment, the M_(n) ranges fromabout 15,000 g/mol to about 200,000 g/mol. In yet another embodiment,the M_(n) ranges from about 20,000 g/mol to about 100,000 g/mol. Instill a further embodiment the M_(n) ranges from about 40,000 g/mol toabout 80,000 g/mol

In some embodiments, the hollow fiber membrane comprises apolyarylethernitrile blended with at least one additional polymer, inparticular, blended with or treated with one or more agents known forpromoting biocompatibility. The polymer may be blended with thepolyarylethernitrile to impart different properties such as better heatresistance, biocompatibility, and the like. Furthermore, the additionalpolymer may be added to the polyarylethernitrile during the membraneformation to modify the morphology of the phase inverted membranestructure produced upon phase inversion, such as asymmetric membranestructures. In addition, at least one polymer that is blended with thepolyarylethernitrile may be hydrophilic or hydrophobic in nature. Insome embodiments, the polyarylethernitrile is blended with a hydrophilicpolymer.

The hydrophilicity of the polymer blends may be determined by severaltechniques known to those skilled in the art. One particular techniqueis that of determination of the contact angle of a liquid such as wateron the polymer. It is generally understood in the art that when thecontact angle of water is less than about 40-50° C., the polymer isconsidered to be hydrophilic, while if the contact angle is greater thanabout 80°, the polymer is considered to be hydrophobic.

One hydrophilic polymer that may be used is polyvinylpyrrolidone (PVP).In addition to, or instead of, polyvinylpyrrolidone, it is also possibleto use other hydrophilic polymers which are known to be useful for theproduction of membranes, such as polyoxazoline, polyethyleneglycol,polypropylene glycol, polyglycolmonoester, copolymers ofpolyethyleneglycol with polypropylene glycol, water-soluble cellulosederivatives, polysorbate, polyethylene-polypropylene oxide copolymersand polyethyleneimines. PVP may be obtained by polymerizing aN-vinylpyrrolidone using standard addition polymerization techniquesknown in the art. One such polymerization procedure involves the freeradical polymerization using initiators such as azobisisobutyronitrile(AIBN), optionally in the presence of a solvent. PVP is alsocommercially available under the tradenames PLASDONE® from ISP COMPANYor KOLLIDON® from BASF. Use of PVP in hollow fiber membranes isdescribed in U.S. Pat. Nos. 6,103,117, 6,432,309, 6,432,309, 5,543,465,incorporated herein by reference.

When the membrane comprises a blend of the polyarylethernitrile and PVP,the blend comprises from about 1% to about 80% polyvinylpyrrolidone inone embodiment, preferably 5-50%, and from about 2.5% to about 25%polyvinylpyrrolidone based on total blend components in anotherembodiment.

PVP may be crosslinked by known methods prior to use to avoid eluting ofthe polymer with the medium. U.S. Pat. No. 6,432,309, and U.S. Pat. No.5,543,465, the disclose methods for crosslinking PVP. Some exemplarymethods of crosslinking include, but are not limited to, exposing it toheat, radiation such as X-rays, ultraviolet rays, visible radiation,infrared radiation, electron beams; or by chemical methods such as, butnot limited to, treating PVP with a crosslinker such as potassiumperoxodisulfate, ammonium peroxopersulfate, at temperatures ranging fromabout 20° C. to about 80° C. in aqueous medium at pH ranges of fromabout 4 to about 9, and for a time period ranging from about 5 minutesto about 60 minutes. The extent of crosslinking may be controlled, bythe use of a crosslinking inhibitor, for example, glycerin, propyleneglycol, an aqueous solution of sodium disulfite, sodium carbonate, andcombinations thereof.

The hydrophilicity of the polymer blends may be determined by severaltechniques known to those skilled in the art. One particular techniqueis that of determination of the contact angle of a liquid such as wateron the polymer. It is generally understood in the art that materialsexhibiting lower contact angles are considered to be more hydrophilic.

In other embodiments, the polyarylethernitrile is blended with anotherpolymer. Examples of such polymers that may be used include polysulfone,polyether sulfone, polyether urethane, polyamide, polyether-amide, andpolyacrylonitrile.

In one particular embodiment, the at least one additional polymercontains an aromatic ring in its backbone and a sulfone moiety as well.These polymers include polysulfones, polyether sulfones orpolyphenylenesulfones or copolymers therefrom. Such polymers aredescribed in U.S. Pat. Nos. 4,108,837, 3,332,909, 5,239,043 and4,008,203. Examples of commercially available polyethersulfones areRADEL R® (a polyethersulfone made by the polymerization of4,4′-dichlorodiphenylsulfone and 4,4′-biphenol), RADEL A® (PES) andUDEL® (a polyethersulfone made by the polymerization of4,4′-dichlorodiphenylsulfone and bisphenol A), both available fromSolvay Chemicals.

The membranes for use in the methods and apparatus of the presentinvention may be made by processes known in the art. Several techniquesfor membrane formation are known in the art, some of which include, butare not limited to: dry-phase separation membrane formation process inwhich a dissolved polymer is precipitated by evaporation of a sufficientamount of solvent to form a membrane structure; wet-phase separationmembrane formation process in which a dissolved polymer is precipitatedby immersion in a non-solvent bath to form a membrane structure; dry-wetphase separation membrane formation process which is a combination ofthe dry and the wet-phase formation processes; thermally-inducedphase-separation membrane formation process in which a dissolved polymeris precipitated or coagulated by controlled cooling to form a membranestructure. Further, after the formation of a membrane, it may besubjected to a membrane conditioning process or a pretreatment processprior to its use in a separation application. Representative processesmay include thermal annealing to relieve stresses or pre-equilibrationin a solution similar to the feed stream the membrane will contact.

Without being bound to theory, it is understood that dialysis works onthe principle of the diffusion of solutes across a porous membrane.During dialysis, a feed fluid that is to be purified passes on one sideof a membrane, and a dialysis fluid is passed on the other side of themembrane. By altering the composition of the dialysis fluid, aconcentration gradient of undesired solutes is formed such that there isa lesser concentration of the undesired solute in the dialysis fluid ascompared to the feed fluid. Thus, the undesired solutes will passthrough the membrane while the rest of the solutes pass through with thenow purified fluid. The membrane may also be designed to have specificpore sizes so that solutes having sizes greater than the pore sizes maynot be able to pass through. Pore size refers to the radius of pores inthe active layer of the membrane. Pore size of membranes according tothe present invention ranges from about 0.5 to about 100 nm, preferablyfrom about 4 to about 50 nm, more preferably from about 4 to about 25nm, even more preferably from about 4 to about 15 nm, and even morepreferably from about 5.5 to about 9.5 nm.

A dialysis apparatus generally comprises a plurality of hollow fiber(HF) membranes that are stacked or bundled together to form a module.The fluid to be purified is fed into the feed line, which is thenallowed to pass through the dialysis lines, while coming in contact withthe membranes. On the other side of the membranes, the dialysis fluid isallowed to pass. The feed fluid may also be pumped under pressure, thuscausing a pressure differential between the feed fluid and the dialysisfluid. During the contact, the concentration gradient between the feedfluid and the dialysis fluid and the membrane pore size causesundesirable solutes to diffuse through the membranes, while the fluidpasses through towards the fluid outlet as the permeate, and theundesirable solutes come out through the retentate line. The solutes inthe dialysis fluid may be chosen in such a way to effect efficientseparation of only specific solutes from the feed fluid.

General methods for preparation of porous hollow fibers and dialysismodules are described in U.S. Pat. No. 6,103,117 incorporated herein byreference. Hemofiltration/hemodialysis modules and their manufacture arealso described in U.S. Pat. No. 5,202,023, which is incorporated hereinby reference. Fabrication of hemofiltration/hemodialysis modulesmembranes is also described in U.S. Pat. No. 4,874,522, 5,232,6015,762,798 5,879,554 and 6,103,117, all of which are incorporated hereinby reference.

Hemodialysis is one instance of dialysis wherein blood is purified byusing a hemodialysis apparatus. In hemodialysis, a patient's blood ispassed through a system of tubing via a machine to the membrane, whichhas dialysis fluid running on the other side. The cleansed blood is thenreturned via the circuit back to the body. It is one object of theinvention to provide hollow fiber membranes for a hemodialysis unit.

DEFINITIONS

The present invention may be understood more readily by reference to thefollowing detailed description of preferred embodiments of the inventionand the examples included therein. In the following specification andthe claims which follow, reference will be made to a number of termswhich shall be defined to have the following meanings:

The singular forms “a”, “an” and “the” include plural referents unlessthe context clearly dictates otherwise.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where the event occurs and instances where it does not.

As used herein, the term “aromatic radical” refers to an array of atomshaving a valence of at least one comprising at least one aromatic group.The array of atoms having a valence of at least one comprising at leastone aromatic group may include heteroatoms such as nitrogen, sulfur,selenium, silicon and oxygen, or may be composed exclusively of carbonand hydrogen. As used herein, the term “aromatic radical” includes butis not limited to phenyl, furanyl, thienyl, naphthyl, and biphenylradicals. The aromatic aryl radical may be substituted. Substituentsinclude a member or members selected from the group consisting of F, Cl,Br, I, alkyl, aryl, amide, sulfonamide, hydroxyl, aryloxy, alkoxy,thioalkoxy, thioaryloxy, carbonyl, sulfonyl, carboxylate, carboxylicester, sulfone, phosphonate, sulfoxide, urea, carbamate, amine,phosphinyl, nitro, cyano, acylhydrazide, hydrazide, imide, imine,amidates, amidines, oximes, peroxides, diazo, and azide.

As used herein the term “aliphatic radical” refers to an organic radicalhaving a valence of at least one consisting of a linear or branchedarray of atoms both cyclic and non-cyclic. Aliphatic radicals aredefined to comprise at least one carbon atom. The array of atomscomprising the aliphatic radical may include heteroatoms such asnitrogen, sulfur, silicon, selenium and oxygen or may be composedexclusively of carbon and hydrogen. For convenience, the term “aliphaticradical” is defined herein to encompass, as part of the “linear orbranched array of atoms which is not cyclic” organic radicalssubstituted with a wide range of functional groups such as alkyl groups,alkenyl groups, alkynyl groups, F, Cl, Br, I, amide, sulfonamide,hydroxyl, aryloxy, alkoxy, thioalkoxy, thioaryloxy, carbonyl, sulfonyl,carboxylate, carboxylic ester, sulfone, phosphonate, sulfoxide, urea,carbamate, amine, phosphinyl, nitro, cyano, acylhydrazide, hydrazide,imide, imine, amidates, amidines, oximes, peroxides, diazo, azide, andthe like. For example, the 4-methylpent-1-yl radical is a C₆ aliphaticradical comprising a methyl group, the methyl group being a functionalgroup which is an alkyl group. Similarly, the 4-nitrobut-1-yl group is aC₄ aliphatic radical comprising a nitro group, the nitro group being afunctional group. An aliphatic radical may be a haloalkyl group whichcomprises one or more halogen atoms which may be the same or different.Halogen atoms include, for example; fluorine, chlorine, bromine, andiodine. The polymer may contain or be further functionalized withhydrophilic groups, including hydrogen-bond acceptors that have overall,electrically neutral charge.

Any numerical values recited herein include all values from the lowervalue to the upper value in increments of one unit provided that thereis a separation of at least 2 units between any lower value and anyhigher value. As an example, if it is stated that the amount of acomponent or a value of a process variable such as, for example,temperature, pressure, time and the like is, for example, from 1 to 90,preferably from 20 to 80, more preferably from 30 to 70, it is intendedthat values such as 15 to 85, 22 to 68, 43 to 51, 30 to 32 etc. areexpressly enumerated in this specification. For values that are lessthan one, one unit is considered to be 0.0001, 0.001, 0.01 or 0.1 asappropriate. These are only examples of what is specifically intendedand all possible combinations of numerical values between the lowestvalue and the highest value enumerated are to be considered to beexpressly stated in this application in a similar manner.

Asymmetric membrane refers to a membrane that is constituted of two ormore structural planes of non-identical morphologies. Dialysis refers toa process effected by one or more membranes in which transport is drivenprimarily by pressure differences across the thickness of the one ormore membrane. Hemodialysis refers to a dialysis process in whichbiologically undesired and/or toxic solutes, such as metabolites andby-products are removed from blood. Molecular-weight cutoff refers tothe molecular weight of a solute below which about 90% of the solute isrejected for a given membrane.

EXAMPLES General Methods and Procedures

Chemicals were purchased from Aldrich and Sloss Industries and used asreceived, unless otherwise noted. All reactions with air- and/orwater-sensitive compounds were carried out under dry nitrogen usingstandard Schlenk line techniques. NMR spectra were recorded on a BrukerAvance 400 (¹H, 400 MHz) spectrometer and referenced versus residualsolvent shifts. Molecular weights are reported as number average (M_(n))or weight average (M_(w)) molecular weight and were determined by gelpermeation chromatography (GPC) analysis on a Perkin Elmer Series 200instrument equipped with UV detector. Polystyrene molecular weightstandards were used to construct a broad standard calibration curveagainst which polymer molecular weights were determined. The temperatureof the gel permeation column (Polymer Laboratories PLgel 5 μm MIXED-C,300×7.5 mm) was 40° C. and the mobile phase was chloroform withisopropanol (3.6% v/v). Polymer thermal analysis was performed on aPerkin Elmer DSC7 equipped with a TAC7/DX thermal analyzer and processedusing Pyris Software. Glass transition temperatures were recorded on thesecond heating scan.

Contact angle measurements were taken on a VCA 2000 (Advanced SurfaceTechnology, Inc.) instrument using VCAoptima Software for evaluation.Polymer films were obtained from casting a thin film from an appropriatesolution (DMAc, chloroform) onto a clean glass slide and evaporation ofthe solvent. Advancing contact angles with water (73 Dynes/cm) weredetermined on both sides of the film (facing air and facing glassslide). Consistently lower values were obtained on the side facing theglass slide presumably due to the smoother surface.

Example 1 Polycyanosulfone (Homopolymer)

Under nitrogen atmosphere N,N-dimethylacetamide (DMAc) (500 mL) andK₂CO₃ (400.08 g, 2.8949 mol) were charged into a 5000 mL-reactor.Bisphenol-S (361.90 g, 1.4460 mol) was added and rinsed in with DMAc(1100 mL). Over the course of 2 days about 2350 mL of toluene was addedin portions and distilled out to dry the reaction mixture. Then,2,6-difluorobenzonitrile (196.85 g, 1.4151 mol) plus more toluene (525mL) was added. During the subsequent polymerization toluene keptdistilling at a constant rate (˜2.5 ml/min). After 5 h, the Mw=80 k(PDI=1.6) was high enough and the mixture was diluted with DMAc (3200mL) and the polymer was drained from the reactor, precipitated intowater, filtered and rinsed with water. The resulting white fluffy powderwas reslurried with water, filtered and slurried again with methanol.After filtration and drying in the vacuum oven 450 g (89% yield) of afluffy white powder was obtained.

-   DSC: T_(g)=227° C.-   TGA: 1-2% weight loss up to 450° C., decomposition starts at 460°    C., 52% wt loss at 900° C.

The cyanosulfone DS430 was dissolved in NMP to produce a 20 weight %solids. To one solution there was added 20 weight %Polyvinylpyrollidinone (Mn=100,000). Both solutions were cast onto aglass plate using a 10 mil casting knife. Porous membranes were producedby immersing the films immediately into water.

Example 2 Hydrophobic/Hydrophilic Block Copolymers

Hexafluorobisphenol A, 2,2-bis(4-hydroxyphenyl)hexafluoropropane,(4.6419 g, 13.8055 mmol), bis(4-fluorophenyl)sulfone (2.8076 g, 11.0424mmol), K₂CO₃ (5.7271 g, 41.4389 mmol), dimethyl acetamide (DMAc) (34.6g) and toluene (18.3 g) were combined in the reaction flask under Argonand immersed into a hot oil bath (150° C.). Under mechanical stirringtoluene/water was distilled off and the progress of the polymerizationwas monitored by GPC. After 6 h, a weight average molecular weight ofapproximately 10,000 was reached and bisphenol S,bis(4-hydroxyphenyl)sulfone, (3.4550 g, 13.8048 mmol),2,6-difluorobenzonitrile (2.3050 g, 16.5703 mmol) and some more toluene(15 mL) were added to the mixture. During the course of thepolymerizations three more aliquots of toluene (5 mL each) were added tofacilitate the removal of water. After a temporary molecular weight dropright after the addition of the second pair of monomers the molecularweight sharply increased until it leveled off at around Mw=41,000.

The polymerization mixture was diluted with DMAc (81 g) and thenprecipitated in water (2×700 mL), filtered, rinsed with methanol andvacuum oven dried.

-   DSC: T_(g)=198° C.-   Contact angle: 92° on top, 70° facing glass slide

Example 3 Hydrophobic/Hydrophilic Block Copolymer, Longer Blocks

Hexafluorobisphenol A, 2,2-bis(4-hydroxyphenyl)hexafluoropropane,(5.0546 g, 15.0330 mmol), bis(4-fluorophenyl)sulfone (3.4405 g, 13.5316mmol), K₂CO₃ (6.2400 g, 45.1501 mmol), dimethyl acetamide (DMAc) (41 g)and toluene (23 mL) were combined in the reaction flask under nitrogenand immersed into a hot oil bath (155° C.). Under mechanical stirringtoluene/water was distilled off and the progress of the polymerizationwas monitored by GPC. After 6 h, a weight average molecular weight ofapproximately 14,000 was reached and bisphenol S,bis(4-hydroxyphenyl)sulfone, (3.6960 g, 14.7678 mmol),2,6-difluorobenzonitrile (2.2677 g, 16.3021 mmol) and some more toluenewere added to the mixture. During the course of the polymerizations morealiquots of toluene were added to facilitate the removal of water. Afterthe addition of the second pair of monomers the molecular weight sharplyincreased until it leveled off at around Mw=68,000 (PDI=6.1).

The polymerization mixture was cooled to 80° C., diluted with DMAc (92g) and then precipitated in water (2×800 mL), filtered, rinsed withethanol and vacuum oven dried.

-   DSC: T_(g)=208° C.-   Contact angle: 90° on top, 59° facing glass slide

Example 4 Hydrophobic/Hydrophilic Block Copolymer

Bisphenol A, 2,2-bis(4-hydroxyphenyl)propane, (25.6187 g, 0.1122 mol),bis(4-chlorophenyl)sulfone (27.6595 g, 0.09632 mol), K₂CO₃ (33.4053 g,0.2417 mol), dimethylsulfoxide (DMSO) (190.5 g) and toluene (100 mL)were combined in the reaction flask under nitrogen and immersed into ahot oil bath (170° C.). Under mechanical stirring toluene/water wasdistilled off and the progress of the polymerization was monitored byGPC. Two more aliquots of toluene (50 mL each) were added after 49 and195 minutes to facilitate the removal of water. After 7 h, a constantweight average molecular weight of approximately 8,500 was reached. Themixture was cooled to room temperature¹ and bisphenol S,bis(4-hydroxyphenyl)sulfone, (12.0352 g, 0.048088 mol),2,6-difluorobenzonitrile (8.9192 g, 0.06412 mol) and more toluene (100mL) were added to the mixture. The mixture was slowly heated back to170° C. to make sure the distillation of toluene/water was not toovigorous. After the addition of the second pair of monomers themolecular weight sharply increased until it leveled off at aroundMw=190,000 (PDI=12.4).

The polymerization mixture was cooled and diluted with DMSO (355 mL) andthen precipitated into water, filtered, rinsed with water and vacuumoven dried at 70° C. A light yellow fluffy powder was obtained (63.7 g).The latter was redissolved in chloroform (595 g) and precipitated intoMeOH (2×2000 mL) to give an almost white precipitate. After air-dryingfor 24 h and vacuum oven (at 70° C.) drying for 3 days 53.2 g (82%) ofan off-white powder were obtained.

-   DSC: T_(g)=202° C.-   Contact angle: 70° (top); 46° (facing glass)

Example 5 Hydrophobic/Hydrophilic Block Copolymer

Bisphenol A, 2,2-bis(4-hydroxyphenyl)propane, (15.0089 g, 65.7447 mmol),bis(4-chlorophenyl)sulfone (14.1515 g, 49.2799 mmol), K₂CO₃ (34.1051 g,0.2468 mmol), dimethylsulfoxide (DMSO) (177 g) and toluene (100 ML) werecombined in the reaction flask under nitrogen and immersed into a hotoil bath (140° C.). (Warning: If bisphenol-S is added at 170° C. a veryintense gas evolution/foaming occurs leading to an uncontrollablesituation.) Under mechanical stirring the mixture was slowly heated to170° C. over the course of 7 hours. Toluene/water was distilled off andthe progress of the polymerization was monitored by GPC. After 9 h, aconstant weight average molecular weight of approximately 4,700 wasreached. The mixture was cooled to room temperature and bisphenol S,bis(4-hydroxyphenyl)sulfone, (24.6847 g, 98.6303 mmol),2,6-difluorobenzonitrile (16.0088 g, 115.0848 mmol) and more toluenewere added to the mixture. The mixture was slowly heated back to 170° C.to make sure the distillation of toluene/water was not too vigorous.After the addition of the second pair of monomers the molecular weightslightly dropped but then immediately sharply increased until it leveledoff at around Mw=65,000 (PDI=4.9).

The polymerization mixture was cooled and diluted with DMSO (343 mL) andthen precipitated into water (2×2000 mL), filtered, rinsed with waterand air dried for 24 hours. After vacuum oven dried at 70° C. for threedays a fluffy powder was obtained (60.5 g).

-   DSC: T_(g)=212° C.-   Contact angle: 72° (top); 31° (facing glass)

Example 6 Random Copolymer

Under nitrogen atmosphere into a 500 mL-reactor, bisphenol-S (19.176 g,84 mmol) and BPA (9.010 g, 36 mmol) were added, which was followed bythe addition of tetramethylene sulfone (95 mL), toluene (100 ml), andK₂CO₃ (24.9 g, 180 mmol). The reaction mixture was heated at 180° C. for8 h to distill the toluene. Bis(4-chlorophenyl)sulfone (20.676 g, 72mmol) and difluorobenzonitrile (6.677 g, 48 mmol) were added. Thereaction temperature was increased to 210° C. After 15 h, the Mw=56 k(PDI=3.8) was high enough and the mixture was diluted with DMAc (150mL). The solution was precipitated in water, and rinsed with water. Theresulting white fluffy powder was reslurried with water, filtered andslurried again with methanol. After filtration and drying in the vacuumoven a fluffy white powder was obtained.

-   DSC: T_(g)=199° C.-   Contact angle: 72° (top); 39° (facing glass)

Example 7 Random Copolymer

Under nitrogen atmosphere into a 500 mL-reactor, bisphenol-S (18.019 g,72 mmol) and BPA (10.958 g, 48 mmol) were added, which was followed bythe addition of tetramethylene sulfone (80 mL), toluene (100 ml), andK₂CO₃ (24.9 g, 180 mmol). The reaction mixture was heated at 180° C. for8 h to distill the toluene. Bis(4-fluorophenyl)sulfone (9.153 g, 36mmol) and difluorobenzonitrile (11.685 g, 84 mmol) were added. Thereaction temperature was increased to 220° C. After 15 h, the Mw=40 k(PDI=2.6) was reached and the mixture was diluted with DMAc (150 mL).The solution was precipitated in water, and rinsed with water. Theresulting white fluffy powder was reslurried with water, filtered andslurried again with methanol. After filtration and drying in the vacuumoven a fluffy white powder was obtained.

-   DSC: T_(g)=209° C.-   Contact angle: 70° (top); 35° (facing glass)

Example 8 Blood Compatibility

Polymer samples 1-5 were fabricated into flat sheet membranes and testedfor contact angle.

Samples #1 through #4 are copolymers using “hydrophobic monomers”(Bisphenol-A, BPA & dichlorodiphenyl sulfone, DCDPS) and “hydrophilicmonomers” (Bisphenol-S, BPS & 2,6-difluorobenzonitrile, DFBN). Polymers#1 and #2 were polymerized in a stepwise manner so that block copolymerswere obtained featuring hydrophobic and hydrophilic blocks as evidencedby NMR spectroscopy. Samples #3 and #4 have the same monomer compositionas #1 and #2, respectively. However the hydrophobic and hydrophilicmonomers in the polymer chain were arranged randomly.

The following table is a summary of monomer composition, polymerarchitectures, contact angles, indicative of the degree of bloodcompatibility:

Sample #1 #2 #3 #4 #5 #6 Architecture Block Block Random Random RandomBlend (1/1) BPA 70% 40% 70% 40% — — BPS 30% 60% 30% 60% 100% 100%  DCDPS60% 30% 60% 30% — 50% DFBN 40% 70% 40% 70% 100% 50% Hydrophobic  8,500 4,600 — — — — block Mw End Mw 190,000 64,000 56,000 40,000 80,000 —T_(g) [° C.]    202   212   199   209   225 224 (est) Contact 46° 31°40-50° 30-40° 30-40° angle

In order to achieve blood compatibility a contact angle of less than40-50° C. is desirable.

It is believed that polymers having microdomains can reduce celladhesion and protein and cell activation when contacted with blood. Suchmicrodomain structures can be achieved by introducing block copolymersthat have hydrophilic and hydrophobic blocks. A microdomain structure ofblock copolymer can offer an optimal condition that can reduce theundesirable effects of hydrophobic surface that have strong adsorptionof proteins and cells. It also reduces undesirable effects caused byhydrophilic surfaces for example platelet adhesion and complementactivation.

While only certain features of the invention have been illustrated anddescribed herein, many modifications and changes will occur to thoseskilled in the art. It is, therefore, to be understood that the appendedclaims are intended to cover all such modifications and changes as fallwithin the true spirit of the invention.

1. A membrane for hemodialysis and hemofiltration having a pore sizebetween about 0.5 nm and 100 nm comprising a polyarylethernitrile havinga contact angle with water of less than about 50° measured on a surfaceof the copolymer cast as a film on a glass substrate and havingstructural units of formula 1, 2, 3 and 4

wherein Z is a direct bond, O, S, SO, SO₂, CO, RPO, alkenyl, alkynyl, aC₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂aromatic radical or a combination thereof; R is a C₆₋₁₂ aromatic radicalor a C₁₋₁₂ aliphatic radical; R¹ and R² are independently H, halo,nitro, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical, or a combination thereof; a is 0, 1, 2 or 3; bis 0, 1, 2, 3 or 4; m and n are independently 0 or 1; Q and Z aredifferent; R³, R⁴ and R⁵ are independently H, halo, nitro, a C₁-C₁₂aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂ aromaticradical or a combination thereof; Q is a direct bond, O, S, alkenyl,alkynyl, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical or a combination thereof; Z¹ is a direct bond,O, S, CH₂, SO, SO₂, CO, RPO or a combination thereof; c, d and e areindependently 0, 1, 2, 3 or 4; p, q and r are independently 0 or 1; andsaid polyarylethernitrile has a benzonitrile content of between about 20and 35 mol %; and the remaining between about 65 and 80 mol % of saidpolyarylethernitrile is made up of Bisphenol-A and Bisphenol-S residues.2. A membrane according to claim 1, wherein the polyarylethernitrilecomprises structural units of formula 1A, 2A, and 3A


3. A membrane according to claim 1, wherein the polyarylethernitrilecomprises structural units of formula 1A, 2A, and 3B


4. A membrane according to claim 1, having a hollow fiber configuration.5. A hollow fiber module comprising a plurality of membranes accordingto claim
 4. 6. A method for hemodialysis and hemofiltration, said methodcomprising contacting blood with a membrane having a pore size betweenabout 0.5 nm and 100 nm comprising at least one polyarylethernitrilehaving a contact angle with water of less than about 50° measured on asurface of the copolymer cast as a film on a glass substrate and havingstructural units of formula 1, 2, 3 and 4

wherein Z is a direct bond, O, S, SO, SO₂, CO, RPO, alkenyl, alkynyl, aC₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂aromatic radical or a combination thereof; R is a C₆₋₁₂ aromatic radicalor a C₁₋₁₂ aliphatic radical; R¹ and R² are independently H, halo,nitro, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical, or a combination thereof; a is 0, 1, 2 or 3; bis 0, 1, 2, 3 or 4; m and n are independently 0 or 1; Q and Z aredifferent; R³, R⁴ and R⁵ are independently H, halo, nitro, a C₁-C₁₂aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂ aromaticradical or a combination thereof; Q is a direct bond, O, S, alkenyl,alkynyl, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical or a combination thereof; Z¹ is a direct bond,O, S, CH₂, SO, SO₂, CO, RPO or a combination thereof; c, d and e areindependently 0, 1, 2, 3 or 4; p, q and r are independently 0 or 1; andsaid polyarylethernitrile has a benzonitrile content of between about 20and 50 mol %; and the remaining between about 50 and 80 mol % of saidpolyarylethernitrile is made up of Bisphenol-A and Bisphenol-S residues.7. A method according to claim 6, wherein the polyarylethernitrilecomprises structural units of formula 1A, 2A, and 3A


8. A method according to claim 6, wherein the polyarylethernitrilecomprises structural units of formula 1A, 2A, and 3B


9. A membrane according to claim 1, wherein the membrane has a hollowfiber configuration.
 10. A dialysis apparatus comprising at least onemembrane having a pore size between about 0.5 nm and 100 nm comprising apolyarylethernitrile having a contact angle with water of less thanabout 50° measured on a surface of the copolymer cast as a film on aglass substrate and having structural units of formula 1, 2, 3 and 4

wherein Z is a direct bond, O, S, SO, SO₂, CO, RPO, alkenyl, alkynyl, aC₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂aromatic radical or a combination thereof; R is a C₆₋₁₂ aromatic radicalor a C₁₋₁₂ aliphatic radical; R¹ and R² are independently H, halo,nitro, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical, or a combination thereof; a is 0, 1, 2 or 3; bis 0, 1, 2, 3 or 4; m and n are independently 0 or 1; Q and Z aredifferent; R³, R⁴ and R⁵ are independently H, halo, nitro, a C₁-C₁₂aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, a C₃-C₁₂ aromaticradical or a combination thereof; Q is a direct bond, O, S, alkenyl,alkynyl, a C₁-C₁₂ aliphatic radical, a C₃-C₁₂ cycloaliphatic radical, aC₃-C₁₂ aromatic radical or a combination thereof; Z¹ is a direct bond,O, S, CH₂, SO, SO₂, CO, RPO or a combination thereof; c, d and e areindependently 0, 1, 2, 3 or 4; and p, q and r are independently 0 or 1.11. A dialysis apparatus according to claim 10, wherein thepolyarylethernitrile comprises structural units of formula 1A, 2A, and3A


12. A dialysis apparatus according to claim 10, wherein thepolyarylethernitrile comprises structural units of formula 1A, 2A, and3B


13. A dialysis apparatus according to claim 10, having a hollow fiberconfiguration.
 14. A dialysis apparatus according to claim 10,comprising a plurality of the membranes.
 15. The membrane of claim 1wherein the membrane has a pore size of between about 4 nm and 25 nm.16. The membrane of claim 15 wherein the membrane has a pore size ofbetween about 4 nm and 15 nm.
 17. The method of claim 6 wherein themembrane has a pore size of between about 4 nm and 25 nm.
 18. The methodof claim 17 wherein the membrane has a pore size of between about 4 nmand 15 nm.